Estradiol(17-beta-estradiol) is a naturally occurring estrogen which is frequently administered to ruminant animals to increase weight gains of the animals. To be effective for increasing weight gains in animals estradiol should be administered at a rate to provide about 50 to 70 micrograms/day/animal.
Feedlot animals are normally maintained at this treatment level for from about 120 days to about 210 days, thus an implant suitable for administration of estradiol should deliver about 50 to 70 micrograms/day/animal with a minimum of variation for up to 200 days without releasing excessive dosages or bursts which can lead to undesirable side effects.
Spherical implant pellets of estradiol having an inert core with the drug in a uniform biocompatable and biosoluble coating of cholesterol, solid polyethylene glycols, high molecular weight fatty acids and alcohols, biosoluble waxes, cellulose derivatives and solid polyvinyl pyrrolidone are described in U.S. Pat. No. 4,096,239.
Cylindrical implants which are not biodegradable, having an inert core which is 2 mm to 10 mm in diameter and 5 mm to 60 mm in length coated with a dimethylpolysiloxane coating, 0.2 mm to 1 mm thick containing 5% to 40% by weight of estradiol in the coating are disclosed in Lilly's U.S. Pat. No. 4,191,741 and their Austrialian Patent Application No. 476,747 describes improvements of this type of implant obtained by washing the implants and coating them with antibiotics or germacides.
Bioabsorbable compositions in particle or pellet form of polylactide-drug mixtures are disclosed in U.S. Pat. No. 3,773,919. The patent describes broadly pharmaceutical depot compositions designed to release effective amounts of drugs over a controlled period of time utilizing a biodegradable polylactide carrier or matrix or polyglycolide or a copolymer of lactide or glycolide containing up to 50% by weight of a comonomer in conjunction with a drug in drug to polymer ratios of from 1%/99% to 99%/1%. The patent also discloses ratios of estradiol to polymer as one part of drug to from 4 to 20 parts of polylactide i.e., from 5% to 25% by weight of estradiol.
It is an object of the invention to provide improved biodegradable compositions which release estradiol in a continuous fashion over extended periods of time and are suitable for parenteral administration to feedlot animals for increasing weight gains of animals. It is another object of this invention to provide improved compositions for administering estradiol parenterally to animals which do not initially or periodically release excessive, undesirable levels of the drug as well as a method for their preparation.